RT Journal Article
SR Electronic
T1 Topological design principle for the robustness of necroptosis biphasic, emergent, and coexistent (BEC) dynamics
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.23.525173
DO 10.1101/2023.01.23.525173
A1 Xu, Fei
A1 Li, Xiang
A1 Wu, Rui
A1 Qi, Hong
A1 Jin, Jun
A1 Liu, Zhilong
A1 Wu, Yuning
A1 Lin, Hai
A1 Shen, Chuansheng
A1 Shuai, Jianwei
YR 2023
UL http://biorxiv.org/content/early/2023/01/24/2023.01.23.525173.abstract
AB Biphasic dynamics, the variable-dependent ability to enhance or restrain biological function, is prevalent in natural systems. Accompanied by biphasic dynamics, necroptosis signaling dominated by RIP1 also appears emergent and coexistent dynamics. Here, we identify the RIP1-RIP3-C8 incoherent feedforward loop embedded with positive feedback of RIP3 to RIP1 is the core topology, and the scale-free feature of RIP3 peak value dictates necroptosis BEC dynamics. Entropy production is introduced to quantify the uncertainty of coexistent dynamics. RIP3 auto-phosphorylation is further determined as a complementary process for robustly attaining necroptosis BEC dynamics. Through screening all possible two- and three-node circuit topologies, a complete atlas of three-node circuit BEC dynamics is generated and only three minimal circuits emerge as robust solutions, proving incoherent feedforward loop is the core topology. Overall, through highlighting a finite set of circuits, this study yields guiding principles for mapping, modulating, and designing circuits for BEC dynamics in biological systems.Competing Interest StatementThe authors have declared no competing interest.